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Drug Design, Development and Therapy 2015Chronic spontaneous urticaria (CSU) is a disease with significant morbidity and relative prevalence that has important effects on the quality of life (QoL) of those who... (Review)
Review
Chronic spontaneous urticaria (CSU) is a disease with significant morbidity and relative prevalence that has important effects on the quality of life (QoL) of those who suffer from it. Omalizumab is a recombinant humanized anti-immunoglobulin E (IgE) antibody that binds to the Cε3 domain of the IgE heavy chain and prevents it from binding to its high-affinity receptor FcεRI. It has been largely studied in the field of asthma and is currently approved for the treatment of both adult and pediatric (children; >6-year-old) patients. In addition, in recent, well-controlled clinical trials in patients with CSU resistant to antihistamines, add-on therapy with subcutaneous omalizumab significantly reduced the severity of itching, and the number and size of hives, and increased patients' health-related QoL and the proportion of days free from angioedema compared with placebo, with an excellent tolerance. Thus, omalizumab is an effective and well-tolerated add-on therapy for patients with CSU who are symptomatic despite background therapy with H1 antihistamines. In this review, we cover the following points: epidemiology, pathogenesis, assessment of activity, impact on QoL, and treatment of CSU, and finally, we focus on omalizumab in the treatment of CSU including the pharmacokinetic properties and mechanism of action, and use in pregnant women, nursing infants, and children.
Topics: Adolescent; Age Factors; Animals; Child; Chronic Disease; Female; Humans; Infant; Infant, Newborn; Male; Omalizumab; Patient Selection; Pregnancy; Quality of Life; Treatment Outcome; Urticaria
PubMed: 26346472
DOI: 10.2147/DDDT.S56004 -
BMJ Open Sep 2021To assess the efficacy and safety of omalizumab for chronic rhinosinusitis with nasal polyps (CRSwNP) and to identify evidence gaps that will guide future research on... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To assess the efficacy and safety of omalizumab for chronic rhinosinusitis with nasal polyps (CRSwNP) and to identify evidence gaps that will guide future research on omalizumab for CRSwNP.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
A comprehensive search was performed in PubMed, Embase, Web of Science and the Cochrane Library on 13 October 2020.
ELIGIBILITY CRITERIA
Randomised controlled trials (RCTs) comparing omalizumab with placebo, given for at least 16 weeks in adult patients with CRSwNP.
DATA EXTRACTION AND SYNTHESIS
Two independent authors screened search results, extracted data and assessed studies using the Cochrane risk of bias tool. Data were pooled using the inverse-variance method and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed by the χ test and the I statistic.
RESULTS
A total of four RCTs involving 303 participants were identified. When comparing omalizumab to placebo, there was a significant difference in Nasal Polyps Score (MD=-1.20; 95% CI -1.48 to -0.92), Nasal Congestion Score (MD=-0.67; 95% CI -0.86 to -0.48), Sino-Nasal Outcome Test-22 (MD=-15.62; 95% CI -19.79 to -11.45), Total Nasal Symptom Score (MD=-1.84; 95% CI -2.43 to -1.25) and reduced need for surgery (risk ratio (RR)=5.61; 95% CI 1.99 to 15.81). Furthermore, there was no difference in the risk of serious adverse events ((RR=1.40; 95% CI 0.29 to 6.80), adverse events (RR=0.83; 95% CI 0.60 to 1.15) and rescue systemic corticosteroid (RR=0.52; 95% CI 0.17 to 1.61).
CONCLUSIONS
This was the first meta-analysis that identified omalizumab significantly improved endoscopic, clinical and patient-reported outcomes in adults with moderate to severe CRSwNP and it was safe and well tolerated.
PROSPERO REGISTRATION NUMBER
CRD42020207639.
Topics: Adult; Chronic Disease; Humans; Nasal Polyps; Omalizumab; Quality of Life; Randomized Controlled Trials as Topic; Sinusitis
PubMed: 34479933
DOI: 10.1136/bmjopen-2020-047344 -
Archivum Immunologiae Et Therapiae... Jun 2017Food allergy is an important health issue that affects up to 8 % of the population. The management of allergic patients involves allergen avoidance and prompts the... (Review)
Review
Food allergy is an important health issue that affects up to 8 % of the population. The management of allergic patients involves allergen avoidance and prompts the treatment of accidental reactions, as no curative treatment is available so far in routine practice. Oral immunotherapy (OIT) is a promising therapeutic alternative, but it is associated with frequent allergic reactions and cost-effectiveness issues. In hopes of reducing such reactions, a number of trials have used omalizumab, an anti-IgE monoclonal humanized antibody, as adjunctive therapy in OIT. The allergens studied in these omalizumab-enabled OIT trials include peanuts, milk, eggs, or mixes of multiple foods. In this article, we review the major findings from these studies and discuss potential benefits and issues related to omalizumab-enabled OIT. Results from the previous trials suggest that the use of omalizumab could potentially lead to safer and more efficient OIT protocols, by reducing the number and severity of reactions, and increasing allergen tolerance threshold. While more evidence is needed with regard to the maintenance of the long-term tolerance after OIT, omalizumab's potential immunomodulatory role could be of benefit. More studies are needed to further document this new indication for omalizumab.
Topics: Administration, Oral; Allergens; Anaphylaxis; Animals; Antibodies, Monoclonal, Humanized; Clinical Trials as Topic; Combined Modality Therapy; Desensitization, Immunologic; Food; Food Hypersensitivity; Humans; Immune Tolerance; Immunoglobulin E; Omalizumab
PubMed: 27628022
DOI: 10.1007/s00005-016-0420-z -
BioMed Research International 2018Different subsets of asthma patients may be recognized according to the exposure trigger and the frequency and severity of clinical signs and symptoms. Regarding the... (Review)
Review
Different subsets of asthma patients may be recognized according to the exposure trigger and the frequency and severity of clinical signs and symptoms. Regarding the exposure trigger, generally asthma can be classified as allergic (or atopic) and nonallergic (or nonatopic). Allergic and nonallergic asthma are distinguished by the presence or absence of clinical allergic reaction and in vitro IgE response to specific aeroallergens. The mechanisms of allergic asthma have been extensively studied with major advances in the last two decades. Nonallergic asthma is characterized by its apparent independence from allergen exposure and sensitization and a higher degree of severity, but little is known regarding the underlying mechanisms. Clinically, allergic and nonallergic asthma are virtually indistinguishable in exacerbations, although exacerbation following allergen exposure is typical of allergic asthma. Although they both show several distinct clinical phenotypes and different biomarkers, there are no ideal biomarkers to stratify asthma phenotypes and guide therapy in clinical practice. Nevertheless, some biomarkers may be helpful to select subsets of atopic patients which might benefit from biologic agents, such as omalizumab. Patients with severe asthma, uncontrolled besides optimal treatment, notwithstanding nonatopic, may also benefit from omalizumab therapy, although currently there are no randomized double-blind placebo controlled clinical trials to support this suggestion. However, omalizumab discontinuation according to each patient's response to therapy and pharmacoeconomical analysis are questions that remain to be answered.
Topics: Anti-Asthmatic Agents; Asthma; Humans; Omalizumab; Phenotype
PubMed: 30310816
DOI: 10.1155/2018/3254094 -
Medicine Jun 2021It is still controversial in the current literature whether omalizumab is beneficial for children with asthma. Given that there is no high-quality meta-analysis to...
BACKGROUND
It is still controversial in the current literature whether omalizumab is beneficial for children with asthma. Given that there is no high-quality meta-analysis to incorporate existing evidence, the purpose of this protocol is to design a systematic review and meta-analysis of the level I evidence to ascertain whether omalizumab is beneficial and safe for children with asthma.
METHODS
The systematic literature review is structured to adhere to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The following search terms will be used in PUBMED, Scopus, EMBASE, and Cochrane Library databases on June, 2021, as the search algorithm: (omalizumab) AND (asthma) AND (children). The primary outcome is the long-term safety and tolerability of omalizumab. The other outcomes include asthma control, quality of life, use of asthma controller medications, and spirometry measurements and emergency room visits due to asthma, and serum trough concentrations of omalizumab, free and total immunoglobulin E measured. Review Manager software (v 5.3; Cochrane Collaboration) will be used for the meta-analysis.
RESULTS
The review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings.
REGISTRATION NUMBER
10.17605/OSF.IO/G6N3P.
Topics: Anti-Asthmatic Agents; Asthma; Child; Emergency Service, Hospital; Humans; Immunoglobulin E; Omalizumab; Quality of Life; Randomized Controlled Trials as Topic; Research Design; Respiratory Function Tests; Meta-Analysis as Topic; Systematic Review as Topic
PubMed: 34087872
DOI: 10.1097/MD.0000000000026155 -
The Journal of Clinical Investigation Aug 2022Over the last 2 decades, omalizumab is the only anti-IgE antibody that has been approved for asthma and chronic spontaneous urticaria (CSU). Ligelizumab, a...
Over the last 2 decades, omalizumab is the only anti-IgE antibody that has been approved for asthma and chronic spontaneous urticaria (CSU). Ligelizumab, a higher-affinity anti-IgE mAb and the only rival viable candidate in late-stage clinical trials, showed anti-CSU efficacy superior to that of omalizumab in phase IIb but not in phase III. This report features the antigenic-functional characteristics of UB-221, an anti-IgE mAb of a newer class that is distinct from omalizumab and ligelizumab. UB-221, in free form, bound abundantly to CD23-occupied IgE and, in oligomeric mAb-IgE complex forms, freely engaged CD23, while ligelizumab reacted limitedly and omalizumab stayed inert toward CD23; these observations are consistent with UB-221 outperforming ligelizumab and omalizumab in CD23-mediated downregulation of IgE production. UB-221 bound IgE with a strong affinity to prevent FcԑRI-mediated basophil activation and degranulation, exhibiting superior IgE-neutralizing activity to that of omalizumab. UB-221 and ligelizumab bound cellular IgE and effectively neutralized IgE in sera of patients with atopic dermatitis with equal strength, while omalizumab lagged behind. A single UB-221 dose administered to cynomolgus macaques and human IgE (ε, κ)-knockin mice could induce rapid, pronounced serum-IgE reduction. A single UB-221 dose administered to patients with CSU in a first-in-human trial exhibited durable disease symptom relief in parallel with a rapid reduction in serum free-IgE level.
Topics: Animals; Antibodies, Monoclonal, Humanized; Down-Regulation; Humans; Immunoglobulin E; Mice; Omalizumab; Urticaria
PubMed: 35912861
DOI: 10.1172/JCI157765 -
Annals of Allergy, Asthma & Immunology... Nov 2023Patient adherence to biologic therapies is crucial for clinical benefits. Previous assessments of US patient adherence to severe asthma (SA) biologic therapies have...
BACKGROUND
Patient adherence to biologic therapies is crucial for clinical benefits. Previous assessments of US patient adherence to severe asthma (SA) biologic therapies have relied on health care insurance claims data that have limitations.
OBJECTIVE
To describe real-world, specialist-reported, biologic administration and adherence among US adults with SA.
METHODS
CHRONICLE (ClinicalTrials.gov identifier: NCT03373045) is an ongoing real-world, noninterventional study of patients with SA treated by US subspecialists. Sites report date and location for all biologic administrations. We evaluated biologic (benralizumab, dupilumab, mepolizumab, omalizumab, reslizumab) adherence as the proportion of days covered (PDC) during the first 52 weeks and the mean number of days until patients received the expected number of doses for 13, 26, and 52 weeks of treatment.
RESULTS
A total of 2117 patients received biologic administrations between February 2018 and February 2022. Most patients (84%) received biologic administrations at a subspecialist site. Over time, administrations at specialist sites decreased, whereas at-home administrations increased. The median PDC was 87%; the mean number of days to receive a 52-week (364-day) equivalent number of doses was 423 for all biologics (average delay of 58 days). Dupilumab had the lowest PDC and highest mean delays in dosing across all intervals; better adherence was observed among commercially insured patients.
CONCLUSION
Patients with SA are mostly adherent to biologic therapies. Biologics with shorter dosing intervals and at-home administration had worse adherence, likely because of greater opportunities for delays. Specialist-reported administration data provide a unique perspective on biologic adherence, which may be overestimated for at-home administrations by insurance claims data.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov: NCT03373045.
Topics: Adult; Humans; Asthma; Omalizumab; Biological Products; Anti-Asthmatic Agents
PubMed: 37506846
DOI: 10.1016/j.anai.2023.07.017 -
Mediators of Inflammation 2023The mechanism of action of omalizumab in urticaria is still not literally known. This study examines the serum values of substance P (SP), calcitonin gene-related...
The mechanism of action of omalizumab in urticaria is still not literally known. This study examines the serum values of substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), and interleukin-31 (IL-31) in patients using omalizumab. In this study, 30 patients with chronic spontaneous urticaria (CSU) who were going to be treated with omalizumab and 20 healthy volunteers took part. Demographic data, clinical data, and disease activity scores were noted. For serum SP, CGRP, NPY, and IL-31 values, 10 mL of blood were taken from the patients before starting the treatment, 3 months after the treatment, at the end of the 6th month, and from healthy volunteers all at once. The change in values measured at baseline, 3rd month, and 6th month was analyzed by the Friedman Test. The Mann-Whitney test was used to compare the parameters obtained from the patients and control groups. The significance level was set at =0.05. SP, CGRP, NPY, and IL-31 values were all statistically significantly lower in the CSU patient group compared to the control group. After treatment, the levels of SP and CGRP in the serum went up, and the levels of serum IL-31 went down. These changes were statistically significant. This study supports the view that omalizumab does not only affect IgE receptors but also affects mast cells through other mechanisms. According to our knowledge, this is the first study to show that omalizumab therapy and serum CGRP levels are related.
Topics: Humans; Omalizumab; Calcitonin Gene-Related Peptide; Neuropeptide Y; Substance P; Anti-Allergic Agents; Immunoglobulin E; Treatment Outcome; Chronic Urticaria; Urticaria; Interleukins; Chronic Disease
PubMed: 37795408
DOI: 10.1155/2023/8087274 -
The Journal of Allergy and Clinical... May 2017Asthma is one of the most common chronic diseases of childhood. Allergen sensitization and high frequencies of comorbid allergic diseases are characteristic of severe... (Review)
Review
Asthma is one of the most common chronic diseases of childhood. Allergen sensitization and high frequencies of comorbid allergic diseases are characteristic of severe asthma in children. Omalizumab, an anti-IgE mAb, is the first targeted biologic therapeutic approved for the treatment of moderate-to-severe persistent allergic asthma (AA) that remains uncontrolled despite high-dose inhaled corticosteroids plus other controller medications. Since its initial licensing for use in adults and adolescents 12 years of age and older, the clinical efficacy, safety, and tolerability of omalizumab have been demonstrated in several published clinical trials in children aged 6 to less than 12 years with moderate-to-severe AA. These studies supported the approval of the pediatric indication (use in children aged ≥6 years) by the European Medicines Agency in 2009 and the US Food and Drug Administration in 2016. After this most recent change in licensing, we review the outcomes from clinical trials in children with persistent AA receiving omalizumab therapy and observational studies from the past 7 years of clinical experience in Europe. Data sources were identified by using PubMed in 2016. Guidelines and management recommendations and materials from the recent US Food and Drug Administration's Pediatric Advisory Committee meeting are also reviewed.
Topics: Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Child; Humans; Omalizumab
PubMed: 28477722
DOI: 10.1016/j.jaci.2017.03.002 -
Respiratory Medicine Jul 2019Several monoclonal antibodies (mAbs) (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) are currently approved for the treatment of severe asthma. They... (Review)
Review
Several monoclonal antibodies (mAbs) (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) are currently approved for the treatment of severe asthma. They have complex pharmacokinetic profiles. These profiles are unique in that they are dependent on their structure as well as can be markedly influenced by the biology of their target antigen, but their general behaviour can still be considered a class property, similar to their endogenous IgG counterpart. They cannot be administered by oral route, have a slow distribution into tissue, are metabolized to peptides and amino acids in several tissues but are protected from degradation by binding to protective receptors (the FcRn), which explains their long elimination half-lives. Their clearance is nonlinear because of the saturation of the target-mediated elimination. Also anti-drug antibody (ADA) response and off-target binding, as well as their glycosylation pattern, can influence the pharmacokinetics of mAbs.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Child; Clinical Trials as Topic; Female; Glycosylation; Histocompatibility Antigens Class I; Humans; Immunoglobulin G; Male; Middle Aged; Omalizumab; Receptors, Fc; Severity of Illness Index; Young Adult
PubMed: 31136930
DOI: 10.1016/j.rmed.2019.05.005